Bone marrow mesenchymal stem cells transplantation alleviates brain injury after intracerebral hemorrhage in mice through the Hippo signaling pathway

Xiao, Chen; Xu, Chenghai; Liang, Hong‐Qing; Xi, Zhiyu; Pan, Jiaji; Yang, Yong; Sun, Qiang; Yang, Guo‐Yuan; Sun, Yuhao; Bian, Liuguan

doi:10.18632/aging.103025

Cited by 14 publications

(11 citation statements)

References 47 publications

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“…In mammals, the activation of the Hippo pathway leads to the inactivation of Yes-associated protein (YAP) by large tumor suppressor 1/2 (LATS1/2)-mediated direct phosphorylation. Contrariwise, dephosphorylation of YAP results in its transport into the nucleus and its succeeding interaction with TEA/ATTS domain (TEAD), forkhead box protein O1 (FOXO1), and other transcription factors, and therefore can exert cell proliferation, organ growth, and stem cell self-renewal [ 147 ]. Other studies on murine LPS models demonstrated that transplantation of murine BM-MSCs with downregulated Hippo pathways led to the intensified retention of murine MSC in ARDS lung tissue and their differentiation into alveolar epithelial type II (AE2) cell as a supporter of the alveolus [ 120 ].…”

Section: Application Of Msc Therapy In Immune-mediated Disordersmentioning

confidence: 99%

RETRACTED ARTICLE: Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders

et al. 2021

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Over recent years, mesenchymal stem/stromal cells (MSCs) and their potential biomedical applications have received much attention from the global scientific community in an increasing manner. Firstly, MSCs were successfully isolated from human bone marrow (BM), but in the next steps, they were also extracted from other sources, mostly from the umbilical cord (UC) and adipose tissue (AT). The International Society for Cellular Therapy (ISCT) has suggested minimum criteria to identify and characterize MSCs as follows: plastic adherence, surface expression of CD73, D90, CD105 in the lack of expression of CD14, CD34, CD45, and human leucocyte antigen-DR (HLA-DR), and also the capability to differentiate to multiple cell types including adipocyte, chondrocyte, or osteoblast in vitro depends on culture conditions. However, these distinct properties, including self-renewability, multipotency, and easy accessibility are just one side of the coin; another side is their huge secretome which is comprised of hundreds of mediators, cytokines, and signaling molecules and can effectively modulate the inflammatory responses and control the infiltration process that finally leads to a regulated tissue repair/healing or regeneration process. MSC-mediated immunomodulation is a direct result of a harmonic synergy of MSC-released signaling molecules (i.e., mediators, cytokines, and chemokines), the reaction of immune cells and other target cells to those molecules, and also feedback in the MSC-molecule-target cell axis. These features make MSCs a respectable and eligible therapeutic candidate to be evaluated in immune-mediated disorders, such as graft versus host diseases (GVHD), multiple sclerosis (MS), Crohn’s disease (CD), and osteoarthritis (OA), and even in immune-dysregulating infectious diseases such as the novel coronavirus disease 2019 (COVID-19). This paper discussed the therapeutic applications of MSC secretome and its biomedical aspects related to immune-mediated conditions. Sources for MSC extraction, their migration and homing properties, therapeutic molecules released by MSCs, and the pathways and molecular mechanisms possibly involved in the exceptional immunoregulatory competence of MSCs were discussed. Besides, the novel discoveries and recent findings on immunomodulatory plasticity of MSCs, clinical applications, and the methods required for their use as an effective therapeutic option in patients with immune-mediated/immune-dysregulating diseases were highlighted.

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Section: Application Of Msc Therapy In Immune-mediated Disordersmentioning

confidence: 99%

RETRACTED ARTICLE: Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders

et al. 2021

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“…Our results are consistent with previous studies. After transplantation of MSCs with IronQ in ICH mice, astrocytes underwent astroglial-mesenchymal phenotype switching and became capable of proliferating, and were protected from apoptosis, similarly to previous studies (51,53). However, some studies have suggested that an excessive proliferation of reactive astrocytes leads to glial scar formation, which is harmful to axon growth and neural network reconstruction (54,55).…”

Section: Discussionsupporting

confidence: 69%

Mesenchymal stem cells transplantation combined with IronQ attenuates ICH-induced inflammation response via Mincle/Syk signaling pathway

Yang

Kantapan

Mazhar

et al. 2022

Preprint

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Background Cerebral edema, inflammation, and subsequent neurological defecit, are the common consequences of intracerebral hemorrhage (ICH). Mesenchymal stem cells (MSCs) transplantation had been used as a neuroprotective therapy in nervous system diseases because of its anti-inflammatory effect. However, the survival, viability, and efficacy of MSCs are limited due to the severe inflammatory response after ICH. Therefore, ways to improve the survival and viability of MSCs will provide a hopeful therapeutic efficacy for ICH. Notably, the metal-quercetin complex via coordination chemistry has been verified positively and studied extensively for biomedical applications, including growth-promoting and imaging probes. Previous studies have shown that the iron-quercetin complex (IronQ) has excellent dual functions with a stimulating agent of cell growth and an imaging probe for magnetic resonance imaging (MRI). Therefore, we hypothesized that IronQ could improve the survival and viability of MSCs, displaying the anti-inflammation function in the treatment of ICH, while also label MSCs for their tracking by MRI. This study was designed to investigate the effects of the combined treatment of MSCs with IronQ on inflammation and elucidate their underlying mechanisms. Methods A collagenase I-induced ICH mice model was extablished, which were randomly divided into model group (Model), quercetin gavage group (Quercetin), MSCs transplantation group (MSCs), and MSCs transplantation combined with IronQ group (MSCs + IronQ). Then the neurological deficits score, brain water content (BWC), and the protein expression levels of IL-6, TNF-α, NeuN, MBP, and GFAP were investigated. We measured the protein expression levels of Mincle and its downstream targets. Furthermore, the lipopolysaccharide (LPS)-induced BV2 cells was used to investigate the neuroprotection of conditioned medium of MSCs co-cultured IronQ in vitro. Results We found that the combined treatment improves the inflammation-induced neurological function and BWC by inhibiting the Mincle/Syk signaling pathway in vivo. The conditioned medium of MSCs co-cultured with IronQ decreased inflammation, the protein expression levels of Mincle, and its downstream targets in LPS-induced BV2 cell line. Conclusions These data suggested that the combined treatment plays a synergistic role in ameliorating the consequences of ICH, including neurologic deficits, brain edema, and inflammatory response through the downregulation of the Mincle/syk signaling pathway.

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“…Astrocytes, one of the primary components of glial cells, have also been confirmed to have a reparative function in the injured brain tissue after ICH ( Zhang et al, 2006 ; Chen et al, 2020b ), although adequate research is not recorded. After transplantation of MSCs in ICH mice, astrocytes underwent astroglial–mesenchymal phenotype switching and became capable of proliferating and were protected from apoptosis via downregulation of p-MST1 and p-YAP ( Chen et al, 2020b ). Together, the Hippo pathway-mediated favorable impacts of MSCs can be recognized as a unique therapeutic target in ICH injury ( Chen et al, 2020b ).…”

Section: Mechanisms Of Mesenchymal Stem Cells In Intracerebral Hemorr...mentioning

confidence: 99%

“…After transplantation of MSCs in ICH mice, astrocytes underwent astroglial–mesenchymal phenotype switching and became capable of proliferating and were protected from apoptosis via downregulation of p-MST1 and p-YAP ( Chen et al, 2020b ). Together, the Hippo pathway-mediated favorable impacts of MSCs can be recognized as a unique therapeutic target in ICH injury ( Chen et al, 2020b ). Experiments performed by Chen et al (2020a) also found that transplanting BMSCs led to an elevation of glial fibrillary acidic protein (GFAP), a biomarker of astrocytes, and the level of expression and improved astroglial–mesenchymal phenotype switching and anti-apoptotic abilities through the Cx43/Nrf2/HO-1 axis.…”

Section: Mechanisms Of Mesenchymal Stem Cells In Intracerebral Hemorr...mentioning

confidence: 99%

Mesenchymal Stem Cell Application and Its Therapeutic Mechanisms in Intracerebral Hemorrhage

Yang

Fan

Mazhar

et al. 2022

Front. Cell. Neurosci.

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Intracerebral hemorrhage (ICH), a common lethal subtype of stroke accounting for nearly 10–15% of the total stroke disease and affecting two million people worldwide, has a high mortality and disability rate and, thus, a major socioeconomic burden. However, there is no effective treatment available currently. The role of mesenchymal stem cells (MSCs) in regenerative medicine is well known owing to the simplicity of acquisition from various sources, low immunogenicity, adaptation to the autogenic and allogeneic systems, immunomodulation, self-recovery by secreting extracellular vesicles (EVs), regenerative repair, and antioxidative stress. MSC therapy provides an increasingly attractive therapeutic approach for ICH. Recently, the functions of MSCs such as neuroprotection, anti-inflammation, and improvement in synaptic plasticity have been widely researched in human and rodent models of ICH. MSC transplantation has been proven to improve ICH-induced injury, including the damage of nerve cells and oligodendrocytes, the activation of microglia and astrocytes, and the destruction of blood vessels. The improvement and recovery of neurological functions in rodent ICH models were demonstrated via the mechanisms such as neurogenesis, angiogenesis, anti-inflammation, anti-apoptosis, and synaptic plasticity. Here, we discuss the pathological mechanisms following ICH and the therapeutic mechanisms of MSC-based therapy to unravel new cues for future therapeutic strategies. Furthermore, some potential strategies for enhancing the therapeutic function of MSC transplantation have also been suggested.

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Bone marrow mesenchymal stem cells transplantation alleviates brain injury after intracerebral hemorrhage in mice through the Hippo signaling pathway

Cited by 14 publications

References 47 publications

RETRACTED ARTICLE: Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders

RETRACTED ARTICLE: Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders

Mesenchymal stem cells transplantation combined with IronQ attenuates ICH-induced inflammation response via Mincle/Syk signaling pathway

Mesenchymal Stem Cell Application and Its Therapeutic Mechanisms in Intracerebral Hemorrhage

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